Smith David C, Chay Christopher H, Dunn Rodney L, Fardig Jude, Esper Peg, Olson Karin, Pienta Kenneth J
Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan School of Medicine, Ann Arbor, Michigan 48109, USA.
Cancer. 2003 Jul 15;98(2):269-76. doi: 10.1002/cncr.11494.
Preclinical data suggest that the combination of intravenous (i.v.) paclitaxel, carboplatin, oral etoposide, and oral estramustine (TEEC) has significant activity in patients with advanced, hormone-refractory prostate carcinoma. The authors conducted this clinical trial to evaluate the addition of carboplatin to the three-drug combination of paclitaxel, estramustine, and etoposide (TEE).
Twenty patients with carcinoma of the prostate that was progressing despite hormone therapy were enrolled on this Phase II trial. Patients were treated with oral estramustine, 280 mg three times daily, and oral etoposide, 50 mg/m2, once daily on Days 1-7, with i.v. paclitaxel, 135 mg/m2, over 1 hour followed by carboplatin (area under the curve, 5) on Day 2 of each 21-day treatment cycle. Patients were evaluated for response after three cycles, and three additional cycles were given to responding or stable patients.
Nineteen patients were evaluable for response, and 12 patients had measurable disease at baseline. The measurable response rate was 58% (7 of 12 patients; 95% confidence interval [95% CI], 28-85%), and all of those were partial responses. Eleven patients had decreases >50% from their baseline prostate specific antigen levels during therapy, for a response rate of 58% (95% CI, 34-80%) by this criterion. The median time to disease progression was 5.5 months, with a median survival of 14.2 months. Major toxicities included Grade (according to version 2 of the National Cancer Institute Common Toxicity Criteria) 4 neutropenia in 4 patients, Grade 4 thrombocytopenia in 4 patients, and anemia > or = Grade 3 in 4 patients. One patient had a deep vein thrombosis.
The combination of TEEC was active in patients with hormone-refractory prostate carcinoma. The regimen was tolerable, with primarily hematologic toxicity. The addition of carboplatin to TEE did not appear to add to the efficacy of the three-drug combination of antimicrotubule agents.
临床前数据表明，静脉注射紫杉醇、卡铂、口服依托泊苷和口服雌莫司汀（TEEC）联合用药对晚期激素难治性前列腺癌患者具有显著活性。作者开展了这项临床试验，以评估在紫杉醇、雌莫司汀和依托泊苷（TEE）三药联合方案中加入卡铂的效果。
20例尽管接受了激素治疗但病情仍进展的前列腺癌患者入组了这项II期试验。患者接受口服雌莫司汀治疗，每日3次，每次280 mg，以及口服依托泊苷治疗，每日50 mg/m²，在第1 - 7天给药，同时在每21天治疗周期的第2天静脉注射紫杉醇135 mg/m²，持续1小时，随后静脉注射卡铂（曲线下面积为5）。在三个周期后评估患者的反应，对有反应或病情稳定的患者再给予三个周期的治疗。
19例患者可评估反应，12例患者在基线时有可测量的病灶。可测量反应率为58%（12例患者中的7例；95%置信区间[95%CI]，28 - 85%），且所有反应均为部分缓解。11例患者在治疗期间前列腺特异性抗原水平较基线下降>50%，按此标准反应率为58%（95%CI，34 - 80%）。疾病进展的中位时间为5.5个月，中位生存期为14.2个月。主要毒性包括4例患者出现4级（根据美国国立癌症研究所通用毒性标准第2版）中性粒细胞减少，4例患者出现4级血小板减少，4例患者出现≥3级贫血。1例患者发生深静脉血栓形成。
TEEC联合用药对激素难治性前列腺癌患者具有活性。该方案耐受性良好，主要毒性为血液学毒性。在TEE方案中加入卡铂似乎并未增加抗微管药物三药联合方案的疗效。
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